Proton nuclear magnetic resonance (NMR) imaging is well suited for imaging tissues with high water content. Metal ions with unpaired spin electrons can alter the NMR relaxation times and thus act as contrast agents for NMR imaging. This has the potential of imparting greater diagnostic utility for this exciting new imaging modality by increasing tissue discrimination. We propose to investigate the NMR relaxation times of intact tissues and of individual intracellular components from normal tissue, disease tissue and tissue altered by pharmacologic manipulation. These studies will be done in the presence and absence of paramagnetic metal ions as potential contrast agents. Delivery of metal ions to specific tissues will be studied both by altering the forms of delivery of metal ion complexes and by altering the affinity of specific tissues by pharmacologic and physiologic manipulation. Microelemental analysis of tissues will provide quantitative data which will be essential for understanding contrast enhancement of NMR images and for advancing knowledge of trace metal biology. Data obtained will provide the basis for understanding how changes in intracellular composition of tissue due to disease or nutrition will be translated to NMR images. These studies will lead to new imaging techniques needed for improving early detection of disease in order to lead to a higher success rate in patient diagnosis, treatment and cure. This project merges two very complex and advanced instrumentations and techniques (NMR imaging and micro X-ray fluorescence spectrometry) through the cooperative contributions of experts in physiology, biology, imaging physics, and imaging for patient diagnosis in order 1) to understand nuclear relaxation of normal and diseased tissues, 2) to develop new NMR imaging techniques for advancing patient diagnosis and well-being, and 3) to elucidate basic trace metal biology which is so critical for maintenance of good health.